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Expression pattern of the thrombopoietin receptor (Mpl) in the murine central nervous system
Anna Ivanova1, Jens Wuerfel, Juan Zhang
1Department of Neonatology, Charité - Universitätsmedizin, Germany.
Background:
Thrombopoietin (Thpo) and its receptor (Mpl), which regulate megakaryopoiesis, are expressed in the central nervous system (CNS), where Thpo is thought to exert pro-apoptotic effects on newly generated neurons. Mpl expression has been analysed in brain tissue on transcript level and in cultured primary rat neurons and astrocytes on protein level. Herein, we analysed Mpl expression in the developing and adult murine CNS by immunohistochemistry and investigated the brain of mice with homozygous Mpl deficiency (Mpl-/-) by MRI.
Results:
Mpl was not detectable at developmental stages E12 to E15 in any resident cells of the CNS. From E18 onwards, robust Mpl expression was found in various brain areas, including cerebral cortex, olfactory bulb, thalamus, hypothalamus, medulla, pons, and the grey matter of spinal cord. However, major developmental changes became obvious: In the subventricular zone of the cerebral cortex Mpl expression occurred only during late gestation, while in the hippocampus Mpl expression was detectable for first time at stage P4. In the white matter of the cerebellum Mpl expression was restricted to the perinatal period. In the adult cerebellum, Mpl expression switched to Purkinje cell. The majority of other Mpl-positive cells were NeuN-positive neurons. None of the cells could be double-labelled with astrocyte marker GFAP. Mpl-/- mice showed no gross abnormalities of the brain.
Conclusions:
Our data locate Mpl expression to neurons at different subdivisions of the spinal cord, rhombencephalon, midbrain and prosencephalon. Besides neuronal cells Mpl protein is also expressed in Purkinje cells of the adult cerebellum.
Insights
The thrombopoietin receptor (Mpl) is expressed in neurons throughout the developing and adult mouse central nervous system (CNS). Mpl expression in the CNS is primarily neuronal, with notable presence in Purkinje cells in adults.
Area of Science:
- Neuroscience
- Developmental Biology
Background:
- Thrombopoietin (Thpo) and its receptor (Mpl) regulate megakaryopoiesis and are found in the central nervous system (CNS).
- Thpo is hypothesized to induce apoptosis in developing neurons within the CNS.
- Previous studies analyzed Mpl expression at the transcript level in brain tissue and protein level in cultured neurons and astrocytes.
Purpose of the Study:
- To investigate Mpl expression patterns in the developing and adult murine CNS.
- To characterize Mpl-expressing cells in the brain using immunohistochemistry.
- To assess the gross brain structure of Mpl-deficient mice using MRI.
Main Methods:
- Immunohistochemistry was employed to analyze Mpl expression in the developing and adult murine CNS.
- Magnetic Resonance Imaging (MRI) was used to examine the brains of Mpl-deficient (Mpl-/-) mice.
- Cellular localization of Mpl was determined by co-labeling with neuronal (NeuN) and astrocyte (GFAP) markers.
Main Results:
- Mpl expression was undetectable in the CNS from embryonic day 12 to 15 but robustly detected from embryonic day 18 onwards.
- Mpl expression exhibited dynamic developmental changes, varying across brain regions and developmental stages.
- Mpl was predominantly found in neurons, including Purkinje cells in the adult cerebellum, and was not detected in astrocytes. Mpl-/- mice displayed no gross brain abnormalities.
Conclusions:
- Mpl protein is expressed in neurons across various CNS subdivisions, including the spinal cord, rhombencephalon, midbrain, and prosencephalon.
- Purkinje cells in the adult cerebellum also express Mpl protein.
- The study clarifies the cellular and temporal distribution of Mpl in the CNS, primarily within neuronal populations.
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